Case report J Korean Child Neurol Soc 2014;22(2):98-101 pISSN 1226-6884

모아모야병 연관 두통 환자에서 뇌 자기공명혈관조영 소견의 악화에 따른 두통 형태의 변화 전남대학교 의과대학 소아과학 교실1, 영상의학교실2, 조선대학교 의과대학 소아과학교실3 이우진1・김영옥1・윤 웅2・노영일3・우영종1

Headache Associated with Moyamoya Disease in a Woo Jin Lee, MD1, Young Ok Kim, MD1, Woong Child: Pain Pattern in MRA Progression Yoon, M.D2, Young Il Rho, M.D3 Young Jong Woo, MD associated with moyamoya disease (HAMD) has been reported in about 20–30% of pediatric cases with moyamoya disease. However, the characteristic Department of Pediatrics1 and Radiology2, Chonnam patterns of HAMD during disease progression are not completely known, although National University Medical School, and Department much is known on the incidence of HAMD and on the treatment effects of bypass of Pediatrics3, School of Medicine, Chosun University, surgery. In a child who presented with HAMD and had no infarction or hemorrhage Gwangju, Republic of Korea till bypass surgery, we described the characteristic patterns of headache progression. At first presentation, the patient complained of severe bilateral headache despite mild stenosis only in the left on magnetic resonance angiography. During all stages of progression, headache was severe and pressing in nature rather than throbbing. Nausea and vomiting were present even in the early stage, but photophobia, phonophobia and neck stiffness developed in the late stage. Headache was aggravated by menstruation and was relieved by analgesics and to­ piramate in the early stage, although the medication failed to provide relief when the headache increased in frequency and duration.

Key Words: Moyamoya disease, Headache, Child

Introduction

Moyamoya disease (MD), a slowly progressive cerebrovascular occlusive disease of the distal internal carotid and cerebral arteries, is characteristically accompanied with puff-like collateral vessels at the base of the brain1-4). According to the report of Submitted: 21 May, 2014 Revised: 20 June, 2014 Kim et al., headache was observed at presentation in 33% of 410 patients with Accepted: 28 June, 2014 pediatric MD5). Headache was the third most common symptoms in pediatric MD following transient ischemic attacks (55.9%) and infarction (39%)5). In their study, Correspondence to Young Ok Kim, MD, PhD Department of Pediatrics, Chonnam National University the Headache associated with moyamoya disease (HAMD) was defined as severe Medical School, 671, Jebongro, Dong-gu, Gwangju, headache, that disturbed daily activity, required rest or medication, and occurred at 501-757, Republic of Korea. least once a month5). Seol et al. also detected HAMD in 21.6% of 204 pediatric Tel +82-62-220-6646, Fax: +82-62-220-6646 E-mail [email protected] patients with MD before surgery6). They observed nausea or vomiting in 27.3% of patients with HAMD, eyeball pain in 6.8% and ab­dominal pain in 4.5%6). Headache was localized only in 11.4% of patients and was provoked in 9.1% by hyperventilation6). Although HAMD has been commonly re­ported by these large Copyright © 2014 by The Korean Child Neurology Society http://www.cns.or.kr http://www.cns.or.kr J Korean Child Neurol Soc 2014;22(2):98-101 99

studies for pediatric MD, the characteristics and classification of were associated with dizziness, weakness or numb­ HAMD are still rarely known5,6). Description of headache pro­ ness in the right upper extremity and ipsilateral side of face. gression based on a headache diary is rare, and clinical charac­ At about 13 years of age, the patient developed a severe head­ teristics of HAMD have been more precisely described only in ache in the early morning with nausea and vomiting. The second several case reports7-12). Herein, we described progressive clinical MRA showed additional stenosis in the right distal ICA, and MCA patterns of headache in a child with HAMD at Suzuki stage 1 to in addition to previous mild stenosis in the left distal ICA and MCA 3 on brain magnetic resonance angiography (MRA). without infarction on brain magnetic resonance imaging (MRI) (Fig. 1B). [99mTc]-ECD brain single photon emission computed tomography showed a perfusion defect in the right parietal and Case report anterior temporal lobes and a decreased vascular reserve in the right parietal, temporal, frontal and left temporal lobes after ace­ A 12-year-old, previously healthy girl developed a sudden, tazolamide administration. Bypass surgery was recommended continuous, severe, pressing, bi-temporal headache. The headache and topiramate (50 mg/day) treatment ameliorated the headaches. was followed by dysarthria, weakness in right hand, and numbness During follow-up up to about 15 years of age, while awaiting in right hand and the ipsilateral side of the face. There was no bypass surgery in another hospital, the patient developed frequent family history of or cerebro-vascular accidents. About headaches followed by transient weakness in her left limbs and a year earlier, she had suffered a similar severe headache, twice ipsilateral eyeball pain. The third MRA at 14 years and 6 months (Table 1). In the first episode, eyeball pain was predominant but of age, showed severe stenosis in the right distal ICA and MCA, an ophthalmologic evaluation showed no abnormality (Table 1). near occlusive stenosis in the left distal ICA and MCA (Fig. 1C), On the first visit to our hospital, brain MRA showed mild stenosis and rich basal collateral vessels (Fig. 1D), without ischemic or in the left distal internal carotid artery (ICA) and M1 portion of hemorrhagic infarction on brain MRI. Headaches were still ag­ the left (MCA) (Fig. 1A). Similar attacks gravated by menstruation. The frequency of headaches increased occurred 4 more times over the next year. Headaches were us­ to 10 times a year and neither NSAID nor preventive topiramate ually bi-temporal, persisting nearly all day long, and aggravated treatment (100 mg/day) was effective in ameliorating the symptoms. during the menstrual period (Table 1). It was occasionally con­ trolled by non-steroidal anti-inflammatory drugs (NSAID) or rest.

Table 1. Characteristics of Headache Associated with Moyamoya Disease in Each Progressive Stage of Magnetic Resonance Angiography 0 month 2 months (2nd 15 months (3rd attack, -26 months -44 months After symptom onset (1st attack) attack) 1st brain image) (2nd brain image) (3rd brain image) Age 10Y9M 10Y11M 12Y (1st visit) 12Y11M 14Y5M Brain MRA stage* in right/left 0 / 1 1/1 3/3 Transient ischemic attack No Yes Yes Yes Yes Weakness - Right upper Right upper Right upper & lower Left upper & lower, Left facial Numbness - Right upper & Right upper & Right upper & - Right facial Right facial Right facial Dysarthria - + + - - Headache Localization - Obscurely bilateral Both temporal Left/right frontal or Both Left temporal or Left temporal, Shoulder & neck occipital Frontal Propagation Eyeball pain +, both - - - +, left Quality Pressing Pressing Pressing Pressing or throbbing Pressing Severity Severe Severe Severe Severe Severe Duration < 12 hr < 12 hr 12~24 hr 12~24 hr 12-24 hr Frequency (/year) 3 4 10 *Probable Suzuki stage on brain magnetic resonance angiography (MRA) is based on MRA generated progressive appearance of moyamoya disease, adapted from angiographic findings from stages one through six, as originally defined by Suzuki and Takaku in 19691). Y, year; M, month; MRA, magnetic resonance angiography. 100 Lee WJ, et al. • Headache with Moyamoya Disease http://www.cns.or.kr

Discussion morrhagic or ischemic) and to which Suzuki stage it belongs. Clinical feature of HAMD may largely differ between pediatric The mechanism underlying HAMD has been suggested to be and adult patients, as the common clinical findings in childhood multifactorial, including a role for cerebral artery nociceptors, MD are recurrent ischemic attacks as opposed to adult presentation the effect of an resulting in stimulation of trigeminal of intracranial hemorrhage1-4). The Suzuki stage (1-6) is associated nociceptors or into the subarachnoid space, neurogenic with progressive angiographic appearance of MD, as originally , and cerebral hypoperfusion7). Although the causal defined by Suzuki and Takaku in 1969 (Table 2)1). Suzuki et al. mechanism for HAMD is still not clearly known, vascular pathology, reported that the degree of change in collateral flow according such as progressive occlusion of intracranial arteries or aneurysm to the stages was only apparent in children but was not in adults1). formation in MD, is suspected as the main eitiology6,7). The nature The apparent collateral flow in children was considered because of HAMD can be presumably different based on the type (he­ they have a greater ability to form collateral vessels than adults1).

Fig. 1. Series of brain magnetic resonance angiography (MRA) images. (A) Initial brain MRA showed mild stenosis (arrow) in the M1 portion of the left middle cerebral artery (MCA). (B) The second brain MRA obtained a year later showed no change in mild stenosis in the M1 of left MCA. MRA also revealed newly seen, diffuse moderate stenosis (short arrows) in the distal supraclinoid portion of right internal carotid artery (ICA) and M1 of the right MCA, and focal severe stenosis (long arrow) at the site of origin of the superior division of the right MCA. (C, D) Follow-up MRA obtained 19 months after the second MRA showed the typical appearance of advanced moyamoya disease; severe stenosis in both the right distal ICA and the right MCA, near occlusive stenosis in both the left distal ICA and the left MCA, and rich collateral vessels from lenticulostriate arteries and posterior cerebral arteries (arrows).

Table 2. Classification of Basal Moyamoya from Suzuki Staging system10) Stage Definition 1 Only carotid fork stenosis without the presence of moyamoya collaterals 2 Initial appearance of basal collateral vessels with all main cerebral arteries dilated 3 Progressive stenosis of the distal ICA, with increasing prominence of the basal collaterals and defection of the middle and anterior cerebral arteries Severe stenosis or occlusion of the anterior circulation with the formation of ECA collaterals in addition to the minimization of moyamoya collaterals 4 and the defection of the posterior cerebral artery 5 Prominence of ECA collaterals, reduction, and stenosis of the basal moyamoya collaterals, and missing main cerebral arteries 6 Complete occlusion of the ICA, disappearance of the basal moyamoya collaterals, with cortical blood supply solely provided though ECA collaterals ICA, internal carotid artery; ECA, external carotid artery. http://www.cns.or.kr J Korean Child Neurol Soc 2014;22(2):98-101 101

Therefore, the characteristics of HAMD can be also different at 뇌출혈이 동반되지 않았던 한 환아에서, 질환이 진행되는 과정 중 관 different ages. 찰된 두통 양상의 특징에 대해서 기술하였다. 환아는 첫 진단 시 양 HAMD can be migraine-like with or without an aura, hemiplegic 측 반구의 심한 두통을 호소하였지만, 뇌 자기공명혈관조영에서는 왼 migraine, episodic tension type headache, or cluster headache6- 쪽 내경동맥의 경한 협착만이 관찰되었다. 두통은 모든 단계에서 매 12). The type of HAMD has been known that can differ in each 우 극심했으며, 박동성이라기보다는 누르는 양상의 두통이었다. 구역 episode, even in the same patient7). Among these types of HAMD, 과 구토는 질환의 초기부터 관찰되었으나, 빛공포, 소리공포 및 경부 the migraine-like headache has been most frequently described 강직은 질환의 후기에 발생하였다. 두통은 월경에 의해 악화되었고 초 6-9). Seol et al. reviewed 204 patients with MD, of which 44 patients 기에는 진통제와 토피라메이트 투약에 호전을 보였으나 빈도와 강도 had HAMD and the clinical pattern of HAMD was mostly similar 가 악화됨에 따라 약제에는 반응하지 않았다. to migraine6). They reported that headache was not ameliorated by the usual preventive or symptom-relieving drugs6). They ob­ served that after bypass surgery, headache persisted in 63% of References the patients with preoperative HAMD and was newly observed in 6.3% of MD patients without previous headache6). 1) Suzuki J, Kodama N. Moyamoya disease—a review. 1983; Here, we described the characteristic patterns of HAMD during 14: 104-9. progression of MD from an early stage in a child. Our case pre­ 2) Takanashi J. Moyamoya disease in children. Brain Dev 2011;33: sented with headache in Suzuki stage 1 on brain MRA, and showed 229-34. 3) Scott RM, Smith ER, Moyamoya disease and moyamoya syndrome. neither infarction nor hemorrhage despite severe headache. This N Engl J Med 2009;360:1226-37. presentation differed from previously reported cases of HAMD 4) Kuroda S, Houkin K. Moyamoya disease: current concepts and with more than Suzuki stage 3 at diagnosis, or with infarction or future perspectives. Lancet Neurol 2008;7:1056-66. hemorrhage. In the current case, obscurely bilateral hemispheric 5) Kim SK, Cho BK, Phi JH, Lee JY, Chae JH, Kim KJ, et al. Pediatric headache was present even with mild stenosis only in the left moyamoya disease: An analysis of 410 consecutive cases. Ann distal ICA and MCA. We were able to clearly observe progression Neurol 2010;68:92-101. of symptoms in HAMD based on the Suzuki stage. HAMD was 6) Seol HJ, Wang KC, Kim SK, Hwang YS, Kim KJ, Cho BK. Headache aggravated by menstruation from Suzuki stage 1. Nausea and in pediatric moyamoya disease: review of 204 consecutive cases. vomiting were observed from Suzuki stage 1, but photophobia, J Neurosurg 2005;103:439-42. phonophobia, and neck stiffness appeared in Suzuki stage 3. 7) Zach V, Bezov D, Lipton RB, Ashina S. Headache associated with moyamoya disease: a case story and literature review. J Headache HAMD was relieved by NSAIDs and topiramate in Suzuki stage 1, Pain 2010;11:79-82. even though they failed in Suzuki stage 3. Over all stages, HAMD 8) Aydin K, Okuyaz C, Gücüyener K, Serdaroğlu A, Akpek S. Moya­ was severe and its nature was pressing more than throbbing. moya disease presented with migraine-like headache in a 4-year- old girl. J Child Neurol 2003;18:361-3. 9) Park-Matsumoto YC, Tazawa T, Shimizu J. Migraine with aura- 요약 like headache associated with moyamoya disease. Acta Neurol Scand 1999;100:119-21. 모야모야병 연관 두통은 소아 모야모야병 환자의 20-30%에서 보 10) Sewell RA, Johnson DJ, Fellows DW. associated 고되어 왔다. 그러나 두통의 빈도와 두통에 대한 우회술의 효과에 대 with moyamoya. J Headache Pain 2009;10:65-7. 해서는 잘 알려진 반면, 병이 진행되는 과정에서 모야모야병 연관 두 11) Bernstein AL. Hemiplegic migraine and moyamoya disease. Am J Dis Child 1993;147:718-9. 통의 임상적 특징에 대한 내용은 잘 알려져 있지 않다. 이에 저자들은 12) Liu X-F, Jung DK. Moyamoya disease and migraine-like headaches. 극심한 두통으로 첫 증상이 발현되었으나, 우회술 전까지 뇌경색이나 Schweiz Arch Neurol Psychiatr 1999;150:272-4.